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Background  Arsenic trioxide (As 2 O 3 ) is highly effective in treating acute promyelocytic leukemia (APL), but shows more variable therapeutic efficacy for other types of hematological malignancies. Previously, we reported that As 2 O 3  selectively eliminates pathogenic B220-expressing T cells in autoimmune MRL/ lpr  mice. We investigated herein the relationship between As 2 O 3  sensitivity of leukemic T-cell lines and the expression levels of the B220 isoform of transmembrane tyrosine phosphatase CD45.    Methods  GSH content, O2 -  production, and B220, HSP70, Fas and FasL membrane expression was measured by flow cytometry. Subcellular localization of B220 was determined by imaging flow cytometry. Cell death was analyzed by morphological changes, annexin V and propidium iodide staining, and caspase 8 and 9 activation. B220 mRNA expression was analyzed by RT-PCR. Activated NF-κB p50 was quantified by a DNA binding ELISA.    Results  We selected human (Jurkat, Jurkat variant J45.01, HPB-ALL) and mouse (EL-4, BW5147, L1210) T-cell lines for their marked differences in As 2 O 3  sensitivity over a large range of doses (1 to 20 μM). Differences in redox status cannot explain the dramatic differences in As 2 O 3  sensitivity observed among the T-cell lines. Unexpectedly, we found that B220 is differentially induced on As 2 O 3 -treated T-cell lines. As 2 O 3  treatment for 24 h induced low (HPB-ALL), intermediate (Jurkat) and high (EL-4, BW5147) levels of B220 membrane expression, membrane-bound HSP70 and cell death, but inhibited NF-κB p50 nuclear translocation. When high levels of B220 expression were achieved with low doses of As 2 O 3 , the T-cell lines died by apoptosis only. When high doses of As 2 O 3  were required to induce B220 expression, leukemic T cells died by both apoptosis and necrosis.    Conclusions  Cellular redox status is not essential for As 2 O 3  sensitivity of leukemic T cells, suggesting the existence of additional factors determining their sensitivity to As 2 O 3  cytotoxicity. Phosphatase B220 could be such a factor of sensitivity. As 2 O 3  treatment inhibits NF-κB p50 nuclear translocation, and induces B220 expression and cell death in a dose and time dependent manner. The levels of B220 induction on leukemic T cells strictly correlate with both the extent and form of cell death, B220 might therefore play a checkpoint role in death pathways.    Electronic supplementary material  The online version of this article (doi:10.1186/1476-4598-13-251) contains supplementary material, which is available to authorized users.

molecular cancer

Sensitivity of leukemic T-cell lines to arsenic trioxide cytotoxicity is dependent on the induction of phosphatase B220/CD45R expression at the cell surface